The human interleukin-2 receptor is being studied to understand critical components of the T cell immune response in normal and neoplastic cells. When T-cells are activated by antigen or mitogenic lectin, both IL-2 and IL-2 receptor expression are induced. IL-2 and IL-2 receptors regulate the magnitude and duration of the T-cell immune response, based on the amount of IL-2 produced, the levels of receptors expressed, and the time course of each of these events. Whereas a low level of intermediate affinity IL-2 receptors are expressed on resting cells, following antigen stimulation, both high and low affinity IL-2 receptor expression is potently induced. Three chains of the IL-2 receptor are now known to exist, namely IL-2Ralpha, IL-2Rbeta, and IL-2Rgamma. This lab was the first to analyze the promoters of each of these genes. In the past year, the group has made major advances: (1) A new enhancer in the IL-2Ralpha 5' regulatory region was delineated. (2) The critical cis-acting elements in the IL-2Rbeta promoter have been delineated and three regions with enhancer activity have been characterized. (3) Major progress has been made in identifying transcription factors responsible for the regulation of expression of both the IL-2Ralpha and IL-2Rbeta chain genes. (4) The IL-2Rgamma gene has been characterized and its promoter identified. (5) An N-terminal region of NF-kappa B p50 and p65 which is critical for DNA binding has been reported. This region contains an interesting motif spanning a critical cysteine which is present in all kappa B binding proteins. Furthermore, the motif is found in zinc finger proteins as well as in NF-kB family proteins, suggesting that this region determines binding specificity of two distinct classes of DNA binding proteins. In NF-kappa B family proteins, the cysteine mediates NF-kappa B binding sensitivity to oxidation/reduction. Such knowledge may be critical in eventually designing therapeutic agents to act as agonists or antagonists of kappa B regulated genes. These findings therefore are critical not only to an understanding of IL-2 receptor gene regulation but also extend to the regulation of other T-cell activation genes.